This is an interdisciplinary approach to study the mechanisms of some of the major disorders which are caused or proved by ultraviolet and visible light, to find ways to prevent them, and to develop new treatment modalities especially exploring the therapeutic possibilities of long-wave ultraviolet light (UV-A, 320-400 nm). A. Prophylaxis of sunburn, solar degeneration, and sun-induced skin carcinoma, by (1) ultraviolet dose response tests that may define the high-risk, skin cancer population; (2) the development of substantive topical agents that protect the skin from sunburn radiation; (3) exploration of a carotenoid, phytoene, a systemic photoprotective agent; (4) experimental induction of tumor formation in animals using newly developed UV-A (320-400 nm) sources. B. Metabolism, mechanism of photosensitivity and clinical use of orally administered psoralens in man: a new high-intensity UV-A source permitting wholebody irradiation in combination with oral psoralens provides an entirely new mode of light therapy that shows promise in the treatment of mycosis fungoides, psoriasis, vitiligo. Studies of the metabolism of psoralens and the determination of monofunctional and bifunctional photoadducts of psoralen and DNA will elucidate the molecular basis of photosensitivity reactions. C. The action spectra of tar photosensitization has finally been defined by the use of a monochromatic laser ultraviolet light; this laser UV-A source and the proposed modifications in our monochromator permit the methods of screening new drugs for phototoxicity. D. Control of disabling photosensitivity associated with erythropoietic protoporphyria (EPP) and polymorphic photodermatosis by oral administration of beta carotene; 56 patients have been successfully treated. This series will be expanded and other photosensitivity disorders included. A study of complement system and singlet oxygen to EPP photosensitivity reactions is proposed. E. Mechanisms of sunburn and melanogenesis will be studied at the cellular, subcellular level using light and electron microscopy and at the molecular level by study of thymine hydrates, DNA-protein cross links, physicochemical changes in DNA and the role of prostaglandins in the sunburn reaction and solar urticaria.